title: Progranulin does not inhibit TNF and lymphotoxin-α signalling through TNF receptor 1.
abstract: Progranulin (proepithelin, granulin precursor) has been recently suggested to exhibit anti-inflammatory properties by directly binding to tumour necrosis factor (TNF) receptors and thereby inhibiting TNF signalling by Tang et al. This finding was challenged by Chen et al. and no interaction between progranulin and TNF receptor (TNFR) 1 or 2 was observed. We tested the ability of recombinant progranulin from different commercial sources to inhibit TNF- or lymphotoxin-α-induced signalling through TNFR1. We observed that progranulin does not affect signalling and cell death induction downstream of TNF or lymphotoxin-α. Our results suggest that the anti-inflammatory role of progranulin is not mediated through direct inhibition of TNFR1.
authors.affiliation: 1] CSCD Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia [2] Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Nima
authors.initials: N
authors.lastname: Etemadi
authors.forename: Andrew
authors.initials: A
authors.lastname: Webb
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Bankovacki
authors.forename: John
authors.initials: J
authors.lastname: Silke
authors.forename: Ueli
authors.initials: U
authors.lastname: Nachbur
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009336:Necrosis; D000077153:Progranulins; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D008233:Lymphotoxin-alpha; D016328:NF-kappa B; D000077153:Progranulins; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases